Release of melanotroph- and corticotroph-type proopiomelanocortin derivatives into blood after administration of corticotropin-releasing hormone in patients with septic shock without adrenocortical insufficiency.

The aim of the study was to assess the adequacy of pituitary function by determining the plasma concentrations of corticotroph-type (corticotropin, beta-endorphin immunoreactive material [beta-END IRM], authentic beta-END, and beta-lipotropin IRM) as well as melanotroph-type (alpha-melanocyte-stimulating hormone [alpha-MSH] and N-acetyl-beta-END [Nac-beta-END] IRM) proopiomelanocortin (POMC) derivatives in patients under septic shock upon administration of corticotropin-releasing hormone (CRH). The objectives were to assess whether an insufficient release of corticotroph- or melanotroph-type POMC derivatives from the pituitary into the cardiovascular compartment correlates with the 28-day mortality rate. Seventeen patients with septic shock but without adrenocortical insufficiency and 16 healthy volunteers were enrolled in the study, and CRH stimulation tests were performed with an i.v. bolus injection of 100 microg human CRH. After treatment with CRH, plasma concentrations of corticotroph-type POMC derivatives increased in survivors and nonsurvivors, melanotroph-type POMC derivatives such as alpha-MSH or Nac-beta-END IRM increased only in survivors in contrast to nonsurvivors. The release of alpha-MSH and Nac-beta-END IRM was suppressed by dexamethasone in survivors but not in nonsurvivors. In patients with septic shock, the response of the pituitary to CRH stimulation in terms of alpha-MSH or Nac-beta-END IRM release was impaired in nonsurvivors compared with survivors or controls. Reduced responses of alpha-MSH or Nac-beta-END IRM to CRH and the invalid suppression by dexamethasone reflect a state of dysfunction of the melanotroph-type POMC system in nonsurvivors. Considering anticytokine and anti-inflammatory effects of alpha-MSH, this dysfunction may increase the risk of death in patients with septic shock.

Balanced anesthesia with remifentanil and desflurane: clinical considerations for dose adjustment in adults.

BACKGROUND: The intraoperative combination of volatile anesthetics with opioids is a well-accepted technique because of its hemodynamic stability and side effects. This study in adults was designed to determine the pharmacodynamic interactions between different dosages of remifentanil and desflurane in response to skin incision. METHODS: A total of 60 patients were enrolled in this study. Patients were prospectively randomized to receive 0, 0.1, 0.15, or 0.25 microg/kg/min remifentanil. Anesthesia was induced with remifentanil, propofol, and succinylcholine. Thereafter, a group-specific desflurane concentration was administered using Dixon's up-and-down technique. After a "wash out" and equilibration period, patients were observed for defense movements up to 1 minute after skin incision. Mean arterial pressure and heart rate were recorded before induction of anesthesia (baseline), at surgical incision, as well as 2 and 4 minutes thereafter. Time until extubation was assessed after stopping desflurane and remifentanil at the end of the surgery. RESULTS: Remifentanil at 0.1, 0.15, or 0.25 microg/kg/min reduced desflurane requirements by 74, 83, and 90 percent, respectively. The time course of mean arterial pressure did not differ between the study groups. However, compared with the group without remifentanil, heart rate was significantly lower in patients receiving 0.15 or 0.25 microg/kg/min remifentanil. No difference between the groups was observed with regard to extubation time. CONCLUSION: Remifentanil reduces in a dose-dependent manner the desflurane requirements for skin incision without increasing recovery time. An infusion rate higher than 0.1 microg/kg/min results in a significantly decreased heart rate.

Response of proopiomelanocortin and gonado- or lactotroph systems to in-vitro fertilisation procedures stress.

OBJECTIVE: To analyse for the first time the response of the corticotroph-type and the melanotroph-type pituitary proopiomelanocortin (POMC) system with regard to in-vitro fertilisation (IVF) treatment using self-developed highly specific non-cross-reacting radioimmunoassay. SETTING: University hospital. patients: A total of 28 patients undergoing IVF oocyte retrieval. Cross sectional exploratory study, one factorial design with repeated measurements on one factor, non-parametric tests. Blood was collected before anaesthesia (t(A)) (n=28) and immediately after oocyte retrieval (t(B)) (n=28). MAIN OUTCOME MEASURE(S): beta-endorphin immunoreactive material (IRM), acetyl-N-beta-endorphin IRM, beta-lipotropin IRM, ACTH, cortisol, estradiol, progesterone, prolactin, luteinizing hormone, and follicle-stimulating hormone. For determination of authentic beta-endorphin [beta-endorphin (1-31)] a highly specific two-site fluid phase immunoprecipitation radioimmunoassay was developed, which did not cross-react with any beta-endorphin derivative or any other opioid peptide tested. RESULTS: No response of acetyl-N-beta-endorphin IRM and of authentic beta-endorphin (1-31) was observed to oocyte retrieval in contrast to a significant increase of corticotroph-type proopiomelanocortin derivatives. A significant rise in prolactin plasma concentration indicates a pronounced lactotroph response to oocyte retrieval stress. No significant correlation between POMC derivates and prolactin and between POMC derivatives and gonadotropins or sexual steroids except for ACTH and progesterone and for beta-endorphin IRM and estradiol was observed. CONCLUSION: IVF treatment stress led to significant corticotroph-type POMC and lactotroph responses, but not to responses of authentic beta-endorphin or melanotroph-type POMC in women undergoing oocyte retrieval.

Sepsis syndrome and death in trauma patients are associated with variation in the gene encoding tumor necrosis factor.

OBJECTIVE: Patients encountering severe trauma are at risk of developing sepsis syndrome and subsequent multiple organ failure. This is often associated with fatal outcome despite survival of the initial injury. We postulate that variation of the gene coding for tumor necrosis factor (TNF)-alpha is associated with increased occurrence of sepsis syndrome and mortality in trauma patients. DESIGN: Prospective cohort study; validation in an external replication sample. SETTING: Tertiary academic medical center. PATIENTS: We included 159 severely traumatized patients from a single center. Serial blood samples were analyzed for serum concentrations of TNF-alpha and lymphotoxin-alpha (LTA). We genotyped nine polymorphisms in the TNF gene and tested for an association with sepsis syndrome and outcome. Genetic associations were validated in an external replication sample (n = 76). We examined the peripheral blood transcriptome in 28 patients by whole genome-based profiling and validated the results. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Carriage of the TNF rs1800629 A allele was associated with higher TNF-alpha serum concentrations on the first day after trauma and during follow-up (two-sided p = 5.0 x 10(-5)), with development of sepsis syndrome (odds ratio 7.14, two-sided p = 1.2 x 10(-6); external validation sample [n = 76]: odds ratio 3.3, one-sided p = .03), and with fatal outcome (odds ratio 7.65, two-sided p = 1.9 x 10(-6)). Carriage of the TNF rs1800629 A allele was associated with differential expression of genes representing stronger proinflammatory and apoptotic responses compared with carriage of the wild-type allele. CONCLUSIONS: Common TNF gene variants are associated with sepsis syndrome and death after severe injury. These findings are strongly supported by functional data and may be important for developing preemptive anti-inflammatory interventions in carriers of the risk-associated allele.

Response to delivery stress is not mediated by beta-endorphin (1-31).

OBJECTIVE: The aim of the study was to determine the reaction of the melanotroph and corticotroph-type pituitary proopiomelanocortin (POMC) response to vaginal delivery and caesarean section stress. Furthermore, the relationship between the release of pituitary POMC fragments, gonadotropins and sexual steroids were examined. STUDY DESIGN: Blood samples were obtained from 10 women in labour on arrival in the birth room (t(A)), at cervix dilatation of 5 cm (t(B)) and immediately after spontaneous delivery (t(C)) and in 16 patients undergoing elective caesarean section before induction of anaesthesia (t(B)) and immediately after delivery (t(C)). Samples were analysed for cortisol, ACTH, authentic beta-endorphin, beta-endorphin immunoreactive material (IRM), acetyl-N-beta-endorphin IRM (NAC), beta-lipotropin (beta-LPH) IRM, oestradiol (E(2)), progesterone (P), prolactin (PRL), FSH and LH. RESULTS: NAC representing the melanotroph-type pituitary POMC system did not increase during the course of caesarean section or spontaneous labour. In contrast, a significant increase of beta-endorphin IRM, beta-LPH IRM and ACTH were observed, representing an activation of the corticotroph-type POMC system. Highly significant correlations between POMC fragment concentrations during caesarean section and spontaneous labour were also observed. Sexual steroids (E(2) and P) decreased significantly. Except for beta-endorphin IRM and E(2) in course of spontaneous delivery no significant correlation was observed between POMC fragment and gonadotropins or sexual steroids. CONCLUSION: Caesarean section and spontaneous delivery activated the corticotroph but not the melanotroph POMC system.

Corrected incidences of co-morbidities - a statistical approach for risk-assessment in anesthesia using an AIMS.

OBJECTIVE: In anesthesia and intensive care logistic regression analysis are often used to generate predictive models for risk assessment. Strictly seen only independent variables should be represented in such prognostic models. Using anesthesia-information-management-systems a lot of (depending) information is stored in a database during the preoperative ward round. The objective of this study was to evaluate a statistical algorithm to process the different dependent variables without losing the information of each variable on patient's conditions. METHOD: Based on data about prognostic models in anesthesia an iterative statistical algorithm was initiated to summarize dependent variables to subscores. Seven subscores out of several preoperative variables were calculated corresponding to the proper incidence and the correlation to the occurrence of intraoperative cardiovascular events was evaluated. After that first step logistic regression was used to build a predictive model out of the seven subscores, 10 patient-related, and two surgery-related variables. Performance of the prognostic model was assessed using analysis of discrimination and calibration. RESULT: Four out of seven subscores together with age, type and urgency of surgery are represented in the prognostic model to predict the occurrence of intraoperative cardiovascular events. The prognostic model demonstrated good discriminative power with an area under the ROC curve (AUC) of 0.734. CONCLUSION: Due to reduced calibration, the clinical use of the prediction model is limited.

Summative software evaluation of a therapeutic guideline assistance system for empiric antimicrobial therapy in ICU.

OBJECTIVE: While developing the patient data management system ICUData in close cooperation with the software company (IMESO GmbH, Hüttenberg, Germany), a therapeutic guideline assistance system for empiric antimicrobial therapy in ICU (called "Antibiotic Wizard") could be introduced and integrated into the existing software. After its introduction into clinical routine, the first version was to be tested, checked for usability and compared to other software products with the help of the IsoMetrics(s) inventory (based on the EN ISO 9241-10 for computer-assisted workflows). METHODS: Half a year after introducing the "Antibiotic Wizard" in the ICUs, 40 physicians from different specialties at different levels of training were surveyed in order to detect deficiencies in the use of the program. The results of these surveys were compared to surveys on the word processing software Word for Windows (WinWord) from Microsoft, the hospital information system IS-H*MED from SAP (online and paper surveys) and the administrative program, SAP R/3 HR, also from SAP. RESULTS: Reliabilities (Cronbach's Alpha) of the subscales ranged from satisfactory (alpha > 0.70) to good (alpha > 0.80), except for "Controllability" (alpha = 0.663) and "Error tolerance" (alpha = 0.693). Medians for individual subscales ranged between 3.04 ("Error tolerance") and 3.96 ("Suitability for learning"). The "Antibiotic Wizard" showed significantly better results compared to both IS-H*MED and SAP R/3 HR in the subscales of "Suitability for the task", "Self-descriptiveness" and "Suitability for learning". In contrast, "Self-descriptiveness" "Controllability" and "Error tolerance" were significantly worse compared to WinWord. CONCLUSIONS: In generally, the usability of the "Antibiotic Wizard" was deemed good. Some weaknesses were found in the fields of "Error tolerance" and "Controllability". These problems will be corrected in future versions.

Increased seroprevalence of parvovirus B 19 IgG in complex regional pain syndrome is not associated with antiendothelial autoimmunity.

The etiology of complex regional pain syndrome (CRPS) is unclear yet. Recently autoantibodies and antecedent viral infections have been discussed to be involved in the pathogenesis of CRPS. We investigated sera from 39 CRPS patients and healthy controls for parvovirus B19 IgG and the occurrence of antiendothelial autoantibodies (AECA). CRPS patients showed a higher seroprevalence of parvovirus B19 IgG than controls (p < 0.01). All CRPS 2 patients were positive. 10.2% of the CRPS patients and 10.0% of the controls had AECA (n.s.) and AECA were not associated with parvovirus B19 seropositivity. Our findings suggest the involvement of parvovirus B19, but not autoantibody-mediated endothelial cell damage, in the pathogenesis of CRPS.

Continuous SvO2 measurement in infants undergoing congenital heart surgery--first clinical experiences with a new fiberoptic probe.

BACKGROUND: SvO2-guided therapy, using fiberoptic oximetric catheters can help to improve the outcome after complex congenital heart surgery especially in infants undergoing the Stage 1-Norwood-Procedure. So far, fiberoptic catheters have to be placed transthoracically by the surgeon into the vena cava or the pulmonary artery putting the infant at an additional risk of bleeding at the time of catheter removal. METHODS: We used a new percutaneously applicable fiberoptic probe for continuous monitoring of central venous saturation in three infants undergoing modifications of the Stage 1-Norwood-Procedure (reconstruction of the aortic arch), two in combination with a bidirectional cavopulmonary connection (Glenn shunt), the third with reconstruction of the pulmonary arteries (biventricular repair). The approved clinical monitoring system consisted of a small (2 F) fiberoptic probe and a bed-side-monitor. The probe was inserted via the routine central venous access for such a case. RESULTS: Continuous SvO2 measurement is feasible in infants using the CeVOX system in combination with routine central venous access, and the advantages of continuous monitoring are discussed. CONCLUSIONS: We believe that compared with transthoracically inserted oximetric catheter, the presented percutaneous technique avoids additional risks at the time of catheter removal (i.e. bleeding) and has become part of our standard management.

Performance and customization of 4 prognostic models for postoperative onset of nausea and vomiting in ear, nose, and throat surgery.

OBJECTIVE: To evaluate the performance of 4 published prognostic models for postoperative onset of nausea and vomiting (PONV) by means of discrimination and calibration and the possible impact of customization on these models. DESIGN: Prospective, observational study. SETTING: Tertiary care university hospital. PATIENTS: 748 adult patients (>18 years old) enrolled in this study. Severe obesity (weight > 150 kg or body mass index > 40 kg/m) was an exclusion criterion. INTERVENTIONS: All perioperative data were recorded with an anesthesia information management system. A standardized patient interview was performed on the postoperative morning and afternoon. MEASUREMENTS: Individual PONV risk was calculated using 4 original regression equations by Koivuranta et al, Apfel et al, Sinclair et al, and Junger et al Discrimination was assessed using receiver operating characteristic (ROC) curves. Calibration was tested using Hosmer-Lemeshow goodness-of-fit statistics. New predictive equations for the 4 models were derived by means of logistic regression (customization). The prognostic performance of the customized models was validated using the "leaving-one-out" technique. MAIN RESULTS: Postoperative onset of nausea and vomiting was observed in 11.2% of the specialized patient population. Discrimination could be demonstrated as shown by areas under the receiver operating characteristic curve of 0.62 for the Koivuranta et al model, 0.63 for the Apfel et al model, 0.70 for the Sinclair et al model, and 0.70 for the Junger et al model. Calibration was poor for all 4 original models, indicated by a P value lower than 0.01 in the C and H statistics. Customization improved the accuracy of the prediction for all 4 models. However, the simplified risk scores of the Koivuranta et al model and the Apfel et al model did not show the same efficiency as those of the Sinclair et al model and the Junger et al model. This is possibly a result of having relatively few patients at high risk for PONV in combination with an information loss caused by too few dichotomous variables in the simplified scores. CONCLUSIONS: The original models were not well validated in our study. An antiemetic therapy based on the results of these scores seems therefore unsatisfactory. Customization improved the accuracy of the prediction in our specialized patient population, more so for the Sinclair et al model and the Junger et al model than for the Koivuranta et al model and the Apfel et al model.

Hypobaric hypoxia affects endogenous levels of alpha-keto acids in murine heart ventricles.

Alpha-keto acids have recently been identified as potent regulators of cellular adaptations to hypoxia. Their actual intracellular concentrations under such conditions are unknown. Here, we determined concentrations of alpha-ketobutyrate, alpha-ketoglutarate, alpha-ketoisocaproate, alpha-ketoisovalerate, alpha-keto-beta-methylvalerate, phenylpyruvate, and pyruvate by a recently developed ultra-sensitive fluorescence HPLC method in ventricular myocardium of mice exposed to hypobaric hypoxia for up to 3 weeks. We observed characteristic alterations of cardiac alpha-keto acid concentrations that are specific for individual alpha-keto acids, show significant side differences (right versus left ventricles), and are suited to trigger some of the cardiac metabolic and structural adaptations to chronic hypoxia.

Moderate hypoxia influences excitability and blocks dendrotoxin sensitive K+ currents in rat primary sensory neurones.

Hypoxia alters neuronal function and can lead to neuronal injury or death especially in the central nervous system. But little is known about the effects of hypoxia in neurones of the peripheral nervous system (PNS), which survive longer hypoxic periods. Additionally, people have experienced unpleasant sensations during ischemia which are dedicated to changes in conduction properties or changes in excitability in the PNS. However, the underlying ionic conductances in dorsal root ganglion (DRG) neurones have not been investigated in detail. Therefore we investigated the influence of moderate hypoxia (27.0 +/- 1.5 mmHg) on action potentials, excitability and ionic conductances of small neurones in a slice preparation of DRGs of young rats. The neurones responded within a few minutes non-uniformly to moderate hypoxia: changes of excitability could be assigned to decreased outward currents in most of the neurones (77%) whereas a smaller group (23%) displayed increased outward currents in Ringer solution. We were able to attribute most of the reduction in outward-current to a voltage-gated K+ current which activated at potentials positive to -50 mV and was sensitive to 50 nM alpha-dendrotoxin (DTX). Other toxins that inhibit subtypes of voltage gated K+ channels, such as margatoxin (MgTX), dendrotoxin-K (DTX-K), r-tityustoxin Kalpha (TsTX-K) and r-agitoxin (AgTX-2) failed to prevent the hypoxia induced reduction. Therefore we could not assign the hypoxia sensitive K+ current to one homomeric KV channel type in sensory neurones. Functionally this K+ current blockade might underlie the increased action potential (AP) duration in these neurones. Altogether these results, might explain the functional impairment of peripheral neurones under moderate hypoxia.

Plasma levels of corticotroph-type pro-opiomelanocortin derivatives such as beta-lipotropin, beta-endorphin(1-31), or adrenocorticotropic hormone are correlated with severity of postoperative pain.

BACKGROUND: In the pituitary of lower species, pro-opiomelanocortin is expressed in corticotroph cells of the anterior and in melanotroph cells of the neurointermediate lobe; enzymatic processing in the corticotrophs results in the release of adrenocorticotropic hormone, beta-lipotropin, or beta-endorphin. In the melanotrophs, these fragments are further modified, eg, by N-terminal acetylation. In the human pituitary, these enzyme systems are located within the same cells in the anterior lobe. We studied the reactions of the pro-opiomelanocortin system under preoperative conditions as well as under postoperative pain. METHODS: In 17 patients undergoing hip or knee arthroplasty, we determined plasma concentrations of N-acetyl-beta-endorphin immunoreactive material, authentic beta-endorphin [beta-endorphin(1-31)], adrenocorticotropic hormone, beta-lipotropin immunoreactive material, and cortisol, as well as pain severity rated by the patients using a visual analogue scale before surgery, after surgery but still under spinal anesthesia, under postoperative pain, and 1 day after surgery. RESULTS: Only low levels of N-acetyl-beta-endorphin immunoreactive material were measured in 16 out of 17 patients. High concentrations (1st quartile/median/3rd quartile; pmol/L) of adrenocorticotropic hormone (22.5/55.8/124) and beta-lipotropin immunoreactive material (6.6/34.6/142) were observed under postoperative pain, accompanied by a small increase of beta-endorphin(1-31) concentrations (0.0/6.1/10.9). Preoperatively small but significantly elevated levels of corticotroph-type and melanotroph-type pro-opiomelanocortin derivatives were observed; in contrast, spinal anesthesia suppressed all pro-opiomelanocortin fragment release. Postoperative pain severity correlated with postoperative adrenocorticotropic hormone, beta-lipotropin immunoreactive material, and beta-endorphin(1-31) concentrations. CONCLUSIONS: We conclude that the melanotroph-type pro-opiomelanocortin system is not activated under postoperative pain; the increase of corticotroph-type pro-opiomelanocortin fragment levels is different in quantity and proportion under preoperative conditions or postoperative pain, respectively.

Preoperative concentration of beta-lipotropin immunoreactive material in cerebrospinal fluid: a predictor of postoperative pain?

Levels of beta-endorphin immunoreactive material (IRM) in cerebrospinal fluid (CSF) have been reported to correlate inversely with postoperative morphine requirement. Considering proopiomelanocortin (POMC) derivatives as predictors for sensitivity to postoperative pain, we determined authentic beta-endorphin (beta-endorphin(1-31)), beta-lipotropin IRM, N-acetyl-beta-endorphin IRM and ACTH in CSF of 17 patients undergoing hip or knee arthroplasty, before surgery (t(A)), immediately after termination of propofol infusion and still under spinal anesthesia (t(B)), under postoperative pain (t(C)) and one day after surgery (t(D)); patients rated their severity of pain on a visual analogue scale (VAS) at those four times. In all patients CSF concentrations of N-acetyl-beta-endorphin IRM and beta-lipotropin IRM were found to be increased after terminating the propofol infusion with spinal anesthesia still effective at t(B). Patients did not feel pain at times t(A), t(B) or t(D); however, they reported moderate to considerable pain at t(C). There were no correlations of postoperative pain severity at t(C) with ACTH, beta-endorphin(1-31) or N-acetyl-beta-endorphin IRM concentrations in CSF. In contrast, we observed significant inverse correlations (Spearman's rank correlation coefficients between -0.83 and -0.85, p<0.01) for postoperative pain severity with beta-lipotropin IRM concentrations in CSF at t(C), and, in addition, at t(A), t(B) and t(D); thus, postoperative pain severity appeared to be dependent on a central system controlling sensitivity to pain, linked to a POMC system releasing beta-lipotropin IRM into CSF and already active at times t(A) and t(B). We conclude that beta-lipotropin IRM in CSF might be considered to serve as a predictor of sensitivity to postoperative pain.

Integration of a handheld based anaesthesia rounding system into an anaesthesia information management system.

BACKGROUND: At the University Hospital Giessen, an anesthesia information management system (AIMS) is used for online record keeping of perioperative patient care, but preoperative anaesthesia assessments were still being recorded on paper and subsequently entered into the AIMS. Personal digital assistants (PDAs) seem to be useful instruments to establish a seamless digital anesthesiological documentation. OBJECTIVES: We decided to implement a solution for direct integration of data gathered during the preoperative assessment into the existing data management infrastructure. Parallel to the development of the system, we surveyed the future users to match their wishes and needs as far as possible. SYSTEM DESCRIPTION: A C program embedding the preoperative AIMS' data fields was developed. Data alignment with the Hospital information system (HIS) is controlled by a Java desktop software. The anaesthesiologist completes the available fields at the patient's bedside following the same algorithm and integrity check as the PC version. STATUS REPORT: Overall, 68% of the surveyed physicians supported the implementation of the system. The PDA solution has been available since May 2002. Data replication into the handheld and integration of mobile collected data into the AIMS generally work without problems. The HIS interconnection software converts the PDA file into the AIMS format for further processing. DISCUSSION: The preoperative anaesthetic assessment is a standardised task well suitable for conversion to an electronic data storage medium. Changing from redundant data entry in the OR to direct electronic recording at the patient's bedside seems simply logical. Handheld computers are inexpensive, flexible gadgets to realize this.

Ketamine impairs excitability in superficial dorsal horn neurones by blocking sodium and voltage-gated potassium currents.

Ketamine shows, besides its general anaesthetic effect, a potent analgesic effect after spinal administration. We investigated the local anaesthetic-like action of ketamine and its enantiomers in Na+ and K+ channels and their functional consequences in dorsal horn neurones of laminae I-III, which are important neuronal structures for pain transmission receiving most of their primary sensory input from Adelta and C fibres. Combining the patch-clamp recordings in slice preparation with the 'entire soma isolation' method, we studied action of ketamine on Na+ and voltage-activated K+ currents. The changes in repetitive firing behaviour of tonically firing neurones were investigated in current-clamp mode after application of ketamine. Concentration-effect curves for the Na+ peak current revealed for tonic block half-maximal inhibiting concentrations (IC50) of 128 microM and 269 microM for S(+) and R(-)-ketamine, respectively, showing a weak stereoselectivity. The block of Na+ current was use-dependent. The voltage-dependent K+ current (K(DR)) was also sensitive to ketamine with IC50 values of 266 microM and 196 microM for S(+) and R(-)-ketamine, respectively. Rapidly inactivating K+ currents (K(A)) were less sensitive to ketamine. The block of K(DR) channels led to an increase in action potential duration and, as a consequence, to lowering of the discharge frequency in the neurones. We conclude that ketamine blocks Na+ and K(DR) channels in superficial dorsal horn neurones of the lumbar spinal cord at clinically relevant concentrations for local, intrathecal application. Ketamine reduces the excitability of the neurones, which may play an important role in the complex mechanism of its action during spinal anaesthesia.

An integrated data-warehouse-concept for clinical and biological information.

The development of medical research networks within the framework of translational research has fostered interest in the integration of clinical and biological research data in a common database. The building of one single database integrating clinical data and biological research data requires a concept which enables scientists to retrieve information and to connect known facts to new findings. Clinical parameters are collected by a Patient Data Management System and viewed in a database which also includes genomic data. This database is designed as an Entity Attribute Value model, which implicates the development of a data warehouse concept. For the realization of this project, various requirements have to be taken into account which has to be fulfilled sufficiently in order to align with international standards. Data security and protection of data privacy are most important parts of the data warehouse concept. It has to be clear how patient pseudonymization has to be carried out in order to be within the scope of data security law. To be able to evaluate the data stored in a database consisting of clinical data collected by a Patient Data Management System and genomic research data easily, a data warehouse concept based on an Entity Attribute Value datamodel has been developed.

Realizing a Realtime Shared Patient Chart using a Universal Message Forwarding Architecture.

The goal of this paper is to describe the clinical needs and the informational methodology which led to the realization of a realtime shared patient chart. It is an integral part of the communications infrastructure of the Patient Data Management System (PDMS) ICUData which is in routine use at the intensive care unit (ICU) of the Department for Anesthesiology and Intensive Care Medicine at the University Hospital of Giessen, Germany, since February 1999. ICUData utilizes a four tier system architecture consisting of modular clients, message forwarders, application servers and a relational database management system. All layers communicate with health level seven messages. The innovative aspect of this architecture consists of the interposition of a message forwarder layer which allows for instant exchange of patient data between the clients without delays caused by database access. This works even in situations with high workload as in patient monitoring. Therefore a system with many workstations acts a blackboard for patient data allowing shared access under realtime conditions. Realized first as an experimental feature, it has been embraced by the clinical users and served well during the documentation of more than 18000 patient stays.

Computers in anesthesia and intensive care: lack of evidence that the central unit serves as reservoir of pathogens.

OBJECTIVE: Computers are becoming increasingly visible in operating rooms (OR) and intensive care units (ICU) for use in bedside documentation. Recently, they have been suspected as possibly acting as reservoirs for microorganisms and vehicles for the transfer of pathogens to patients, causing nosocomial infections. The purpose of this study was to examine the microbiological (bacteriological and mycological) contamination of the central unit of computers used in an OR, a surgical and a pediatric ICU of a tertiary teaching hospital. METHODS: Sterile swab samples were taken from five sites in each of 13 computers stationed at the two ICUs and 12 computers at the OR. Sample sites within the chassis housing of the computer processing unit (CPU) included the CPU fan, ventilator, and metal casing. External sites were the ventilator and the bottom of the computer tower. Quantitative and qualitative microbiological analyses were performed according to commonly used methods. RESULTS: One hundred and ninety sites were cultured for bacteria and fungi. Analyses of swabs taken at five equivalent sites inside and outside the computer chassis did not find any significant-number of potentially pathogenic bacteria or fungi. This can probably be attributed to either the absence or the low number of pathogens detected on the surfaces. CONCLUSION: Microbial contamination in the CPU of OR and ICU computers is too low for designating them as a reservoir for microorganisms.